Effects of Adjuvant Dexmedetomidine in Dorsal Penile Block for Penile Prosthesis Implantation

doi:10.21203/rs.3.rs-4893523/v1

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Effects of Adjuvant Dexmedetomidine in Dorsal Penile Block for Penile Prosthesis Implantation

https://doi.org/10.21203/rs.3.rs-4893523/v1

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Inflatable penile prosthesis (IPP) surgery is the gold standard treatment for medication-refractory erectile dysfunction. While satisfaction rates are high, post-operative pain and narcotic requirement remain a concern. Intraoperative dorsal penile nerve block (DPNB) with long-acting local anesthetic can improve analgesia. Recent studies on peripheral nerve blocks in other fields have demonstrated prolonged analgesia and minimal adverse effects with blocks containing local anesthetic and dexmedetomidine. This retrospective study aimed to evaluate the effect of DPNB for IPP surgery with and without dexmedetomidine on postoperative analgesia. This is a single institution retrospective IRB-approved study of patients undergoing IPP surgery with preoperative DPNB and without dexmedetomidine. The DPNB used in the 2019 control group utilized 0.25% bupivacaine, while the 2020–2021 intervention group also included 70 µg dexmedetomidine. The primary outcome was pain scores at post-operative hours 0, 2, 6, 12, 18, and 24, while secondary outcomes were intraoperative and postoperative narcotic use, intraoperative hypotension (IOH), (MAP < 60 for > 5 minutes or requiring intervention), and intraoperative bradycardia, (HR < 50 for > 1 minute). 98 patients met inclusion criteria, 32 in the control group and 66 in the intervention group. 24-hour pain scores were significantly lower in the intervention group (1.1 vs 3.8, 1.6 vs 3.9, 3.1 vs 4.9, 2.4 vs 4.3, 2.9 vs 5.3, 2.3 µg vs 4.4 µg; p < 0.05). Postoperative narcotic requirement was lower for the intervention group (46 vs 65, P < 0.05). Adverse effects (IOH and bradycardia) occurred in 16 intervention cases, each mild and brief. Intraoperative DPNB with local anesthetic and dexmedetomidine can safely improve immediate post-operative analgesia and decrease opioid consumption in the first 24 hours. This type of combination DPNB may be useful for other penile and scrotal surgeries, requiring prospective randomized study.

Inflatable penile prosthesis (IPP) surgery is the gold standard treatment for medication-refractory erectile dysfunction. Dorsal penile nerve block improves local pain control postoperatively and is aided by Tylenol and pain-guided opioids. While narcotics are used as a mainstay of postoperative pain control, in the setting of damaging narcotic overuse and addiction we need alternative anesthetic techniques that decrease their use. Such improved techniques may also decrease patient discomfort, pain and postoperative nausea and vomiting. Since their development in the 1960s ⍺2 agonists have been known to act as powerful sedatives. (ref. 1) Among them Dexmedetomidine is highly specific to ⍺2 adrenergic receptors, with a fast onset time and a short half-life of 2 hours (ref. 2), making them particularly useful for use during procedures. It was also demonstrated that beyond their sedative effects ⍺2 agonists attenuate opioid-induced hyperalgesia. (ref. 3) Meta-analyses of adjuvant dexmedetomidine for brachial plexus blocks demonstrated its ability to improve the duration of intraoperative nerve blocks with the noted risk of hypotension and bradycardia, which should be monitored for when used. (ref. 2, 4, 5) Further analysis demonstrates that adjuvant dexmedetomidine doses above 50 micrograms lower motor and sensory block onset time while increasing sensory and motor block duration. (ref. 5) Its applications are expanding and suggest a potential for improved analgesia after penile prosthesis surgery.

To date, there are no published clinical trials analyzing the impact of this technique for penile prosthesis implantation. As such, we conducted a comparative study to evaluate the efficacy of dexmedetomidine alongside bupivacaine and dexamethasone in improving analgesia and decreasing opioid use after primary penile implant placement.

The study was approved by Boston Medical Center's IRB. Outcomes of patients undergoing primary penile implant in the year 2019 (bupivacaine-only block) were compared to the those of patients undergoing primary penile implant in 2020 and 2021, when dexmedetomidine 1 µg /kg (max 70 µg) and dexamethasone 4mg was routinely added to the 0.25% bupivacaine penile nerve block. (ref. 6) Consent was received preoperatively and all patients were older than 18 years old. Patients were not included in the study if they refused to consent or if they're penile implant was a repair or a non-primary attempt. Patients who were not admitted for at least 24 hours of observation (due to bed availability subsequent to COVID-19) were not included.

All patients underwent primary penile prosthetic implantation by the same surgeon. All patients were informed of the sequence of the procedure. In both groups patients received sedation with general anesthesia and standard penile block technique.

Demographic data, diabetes status, history of opioid overuse suggesting likely opioid insensitivity, patient weight and age were all recorded. In both groups the same multimodal postoperative analgesia was utilized, which included PRN acetaminophen, fentanyl, oxycodone, and hydromorphone. Postoperative pain was recorded every 2 to 3 hours by nursing staff using an Analogue Pain Scale from 0 to 10 (0, no pain, to 10, worst imaginable pain). Pain levels at 0, 2, 6, 12, 18 and 24 hours postoperatively were retrieved from patient charts. When pain levels were not recorded at one of the above time points a pain measure from an immediately adjacent hour was used. Amounts of administered narcotics were split into time windows: first 2 hours, hours 3–6, 7–12, 13–18, and 19–24. Narcotics (fentanyl, oxycodone, hydromorphone) administered were converted to oral morphine equivalents at ratios of 25:3, 2:3, and 1:20 µg, respectively. Secondary outcomes were intraoperative hypotension (IOH) below MAP of 60 for more than 5 minutes, and bradycardia under 50 bpm requiring intervention. Analysis was done with students-t test and an alpha of 0.05 was to be considered statistically significant.

Of the 98 patients included in this study (mean age of 60 years, SD 8.86), 32 (mean age 63, SD 8.9) received the bupivacaine only nerve block and 66 (mean age 59, SD 8.7) received the combination bupivacaine, dexmedetomidine, steroid nerve block. The intergroup differences are summarized in table 1. There is no significant difference between the groups’ ages, diabetes states, or weights. The intervention group had a significantly higher portion of participants with histories of opioid use outside of prescriptions. Pain scores and narcotics usage are summarized in Figs. 1–4.

There was no significant difference in the intraoperative narcotics administered between treatment and control groups (111 (50.2) vs 132 (69.6) oral morphine equivalents, P = 0.13). (Fig. 3). There were 4 instances of IOH with MAPs of 56 mmHg for 15 minutes, 59 for 6 minutes, 53 for 15 minutes, and 53 for 7 minutes, from preop MAPs of 77, 208, 87, and 80, representing decreases in MAP by 20, 49, 34, and 27.

Mean pain levels in the first 24 hours at all time checks (0, 2, 6, 12, 18, 24 hrs) were significantly lower for the combination group than for the bupivacaine-only group. (1.1 vs 3.8, 1.6 vs 3.9, 3.1 vs 4.9, 2.4 vs 4.3, 2.9 vs 5.3, 2.3 vs 4.4, p < 0.01)

Mean narcotic consumption in the 0–2, 2–6, and 13–18 hours postoperative windows were significantly lower for the combination group than for the bupivacaine-only group (7.9 (9.231) vs 13.8 (9.054), p < 0.05). Narcotic consumption for the other time blocks (7–12 and 19–24) were not significantly lower in the intervention group.

Mean total postoperative narcotic consumption was lower for the combination block group (45.8 (30.9) vs 65.4 95CI (37.74) oral morphine equivalents, p < 0.05). (Fig. 4). Of the patients who received the combination block, 4 had intraoperative hypertension (MAP < 60) for more than 5 minutes, while 14 had self-limited bradycardia (< 50 bpm).

The American society of anesthesiologist 2016 guidelines stated that enhanced recovery after surgery (ERAS) is an integral part of future perioperative care and recommends multimodal opioid sparing approaches for management postoperative pain. (ref. 7) Adjuvant dexmedetomidine from 0.2 to 4 µg per kilogram has been studied for its ability to lengthen sensory and motor blockade, decrease postoperative nausea and vomiting, and postoperative opioid requirement. (ref. 8) Peripheral administration, particularly at doses above 50 µg, have been found by many to provide therapeutic effect. (ref. 2) Here we evaluate the effectiveness of 1 µg/kg of dexmedetomidine (max: 70 µg) for adjuvant peripheral anesthesia by a dorsal penile block for primary penile prosthesis implantation where bupivacaine alone is among current standards.

This study’s outcomes align with that of others investigating dexmedetomidine‘s use and pediatric dorsal penile blocks for circumcision and infraumbilical surgeries. (ref. 9) More generally, dexmedetomidine has been shown to be an excellent anesthetic adjuvant in laparoscopic and open procedures including bariatric, major spine and gynecological. (ref. 7) However, procedure-specific efficacy is still being borne out. Meta-analysis of its use within brachial plexus blocks has shown success while evidence thus far shows effectiveness for femoral nerve blocks to be equivocal. (ref. 10, 11, 12)

In addition to reductions in pain and opioid consumption, length of hospital stay is a site of potential improvement with respect to economy of medical resources. Primary penile prosthesis implantation commonly requires a single-night admission for observation which was briefly sacrificed for eligible patients during the beginning of the COVID-19 pandemic at Boston Medical Center due to limited bed availability. The question arises regarding the possible utility of dexmedetomidine in decreased hospital stays and recovery times, and potential adverse effects. A meta-analysis has found no evidence that ⍺2 agonists lengthened recovery times although they are well known for their sedative properties. (ref. 2) The concern for a disadvantageous tradeoff of decreased opioid consumption for increased complications is attenuated by that study’s finding that bradycardia rates, but not hypotension rates, had significantly increased with the use of 50 or more µg of dexmedetomidine and that all cases were either self-limited or easily resolved with atropine.

Dexmedetomidine’s improvement in postoperative analgesia, reduction of perioperative opioids, subsequent reduction of adverse effects of narcotics. Of note, a decrease in postoperative narcotic consumption was no longer observed after hour 18, after which values were nearly identical and suggest that the anesthetic effects of dexmedetomidine wane between hours 18 and 24. Furthermore, spinal block and monitored anesthesia care (MAC) may make same-day discharge more possible. As this is an early study of dexmedetomidine’s use in prosthetic implantation, there remains the need to more thoroughly evaluate its utility for this surgery.

Since completion of this research, we have discontinued the use of dexamethasone to avoid the temporary hyperglycemia that could increase risk of infection and because literature review has shown its non-superiority (ref. 13). Anecdotally, we have not found a subsequent diminished efficacy of the penile block since removing dexamethasone. We have also increased bupivacaine to 0.5% and begun penile and pudendal blocks. We believe that postoperative pain scores have improved further with these changes, though future studies are needed for evaluation. In addition, given anesthesia’s recognition of the efficacy of the dexmedetomidine they have since decreased intraoperative narcotics.

Our study is limited in that it is retrospective and that the concurrent addition of dexamethasone to our block represents a confounding factor. It also lacks data on intraoperative bradycardia and IOH in the control group, which should be evaluated in future studies. Further evaluation by randomized controlled trials of decreased pain, nausea and vomiting, opioid use and hospital stay length is recommended given the potential benefits for patients undergoing primary penile prosthesis implantation.

In summary, adjuvant use of 1 µg/kg (max 70 µg) of dexmedetomidine in dorsal penile block for primary penile prosthesis implantation showed a statistically significant decrease in pain throughout the entire 24hr postoperative period and reduction in opioid use in the first 18 postoperative hrs. Cumulative decreases in postoperative opioid use in all time blocks produced a statistically significant 30% decrease in overall opioid use in the first 24 postoperative hours.

The authors of this study have no conflicts of interest to report.

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Table 1. Patient Demographics

Intergroup Differences
Characteristic	All Participants	Control Group	Intervention Group	P Value
N	98	32 (34%)	66 (67%)
Age in years Mean (range)	60.4 (36 - 83)	62.6 (43 - 81)	59.3 (36 - 83)	0.0948
Diabetes Mellitus	46% (45)	50% (16)	44% (29)	0.5798
Opioid Use History	81.6% (8)	0% (0)	12.1% (8)	0.0039
Weight in kg	88.7 (57 - 134)	90.5 (71 - 134)	87.8 (57 - 115.6)	0.3853
Intraoperative Narcotics (po morphine eq)	117.9 (0 - 250)	132 (0 - 250)	111 (0 - 250)	0.1332

There is NO conflict of interest to disclose.

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Effects of Adjuvant Dexmedetomidine in Dorsal Penile Block for Penile Prosthesis Implantation

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